Is PSIP1 p.Ala484Pro (c.1450G>C) pathogenic?

PSIP1 p.Ala484Pro (c.1450G>C) is classified Likely benign in PSIP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-21). AlphaMissense: likely benign (0.0945); Rare (popmax 0.243%, afr).

How common is PSIP1 p.Ala484Pro (c.1450G>C) in the general population?

PSIP1 p.Ala484Pro (c.1450G>C) is rare (popmax 0.243%, afr) (gnomAD).

What do computational predictors say about PSIP1 p.Ala484Pro (c.1450G>C)?

AlphaMissense predicts likely benign (score 0.0945) — an in-silico prediction, not a clinical call.

PSIP1 p.Ala484Pro

c.1450G>C · rs142155589 · VCV749768

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0945 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.243%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0945	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -6.71	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.36	GERP -0.73, phastCons 0.045
Regional constraint	o/e 1.06	unconstrained · MANE · 24 kb · p 0.18 · regional, not allelic
Overall
CADD	14.97	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.243% African / African-American · 182/74,976 alleles

Filtering AF 0.214% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.013% 210/1,613,192 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.243%	412
Admixed American	0.0234%	4,271
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,246
European (non-Finnish)	0.000254%	393,238

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PSIP1
Protein: p.Ala484Pro
Coding: c.1450G>C
MANE Select: NM_033222
dbSNP: rs142155589
Type: single nucleotide variant
Location: chr9:15466830 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.32 · 40 PDB
Residue 484: the 'disordered' region

Full PSIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PSIP1 c.72+8A>G Benign ★★ same type
PSIP1 p.Gln472Leu Benign ★★ same type
PSIP1 p.Leu478Val Benign ★★ same type
PSIP1 p.Ala185Val Uncertain significance ★ ⚠ same type
PSIP1 p.Ala265Pro Uncertain significance ★ ⚠ same type
PSIP1 p.Ala32Asp Uncertain significance ★ ⚠ same type
PSIP1 p.Ala453Thr Uncertain significance ★ ⚠ same type
PSIP1 p.Arg354Trp Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/psip1-p-ala484pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown